Summary of Work: Telomeres are structures on the ends of linear chromosomes that are required for genome stability. They counterbalance the loss of DNA from a chromosome end due to incomplete DNA replication and they distinguish a natural chromosome end from a broken chromosome end. Drosophila Telomeres lack the simple tandem repeats found at telomeres in most species. Instead, Drosophila ends are maintained by tip specific transposition of a non-LTR retrotransposon. Adjacent to this transposon array is a telomere associated satellite (TAS) that resembles subtelomeric sequences in other species. The TAS repeats are thought to be associated with the formation of heterochromatin and the inactivation of genes placed in their vicinity, and may be instrumental in forming associations with other telomeres, the nuclear matrix and the lamina. Reporter genes placed in TAS are repressed and variegate, that is they are expressed in some cells of the appropriate tissue, but not others. In many cases a reporter gene inserted into TAS is greatly repressed when the homologue is wild type, but less repressed when the reporter is homozygous. Decreased repression is also seen when the homologous telomere is deleted, or when a nonhomologous telomere is disrupted by an insertion into TAS or deleted. We propose that telomeres associate in a ?telocenter?, and that reporter genes placed in the telocenter are repressed. Disruption of the telocenter by insertion of other nontelomeric genes or deletion of one of the components of the telocenter relieves the repression. Sixty-eight transacting modifiers of telomeric repression have been isolated and are being characterized. Similar modifiers of centromeric position effect variegation have been used to identify heterochromatic proteins, but none of these modifiers have an effect on telomeric position effect. This suggests that a new set of telomeric proteins may be identified by the proposed search. - Chromosome Stability, Heterochromatin, Telomere, Drosophila Melanogaster, Gene Expression Regulation